Pathobiology of fungal infections of the central nervous system with special reference to the Indian scenario

Ubiquitously present fungi in the environment find a nidus in the human body and adopt its metabolic machinery to be in symbiosis or become pathogenic. Immunocompromised states like human immunodeficiency virus (HIV) / acquired immunodeficiency syndrome (AIDS), systemic neoplasia and organ transplantation have enhanced the frequency of fungal infections. High-risk behavior, IV drug abuse and air travel have led to the emergence of new fungal infections hitherto geographically localized. The pathology in the central nervous system (CNS) is dictated largely by the size of the fungus - the yeast forms, by virtue of their small size enter the microcirculation to cause meningitis and microabscesses, while hyphal forms invade the vasculature to manifest as large pale or hemorrhagic infarcts. The growth kinetics of fungi, the antigenic character of the capsule. the proteases secreted by the mycelial forms and the biochemical milieu in the host also determine clinical manifestations. A hospital-based analysis of the available information from India suggests that in the non-HIV patient population, hyphal forms like Aspergillosis and Zygomycosis are the most common pathogens, while yeast forms like Cryptococcus and Candida are the prime pathogens in cases of HIV/AIDS, the altered macrophage function acting in synergy with suppressed cell-mediated immunity. In Northeastern states, systemic infection by Penicillium marneffei is reported in association with HIV though CNS involvement is not recorded. Although fungal infections of the CNS are reported from various hospitals in India, studies are limited by non-availability of relevant microbiological studies and the reported prevalence data is biased by the surgical practices, availability of postmortem and microbiology and laboratory support. Detailed clinical and mycological investigations related to the interaction between the fungus and host environment is a fertile area of research to understand the basic pathogenetic mechanisms.

Keywords
Aspergillosis, central nervous system, cryptococcosis, dimorphic fungi, mycotic infections, pathogenesis, penicilliosis, pheohyphomycosis, zygomycosis